Basic research for understanding the molecular mechanism of mental retardation and the development of the treatment and diagnostic methods for the disease.
| Project/Area Number |
18591156
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kochi University |
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Principal Investigator |
MITSUI Shinichi Kochi University, Department of Neurobiology and Anatomy, Associate Professor (20295661)
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| Co-Investigator(Kenkyū-buntansha) |
YURI Kazunari Kochi University, Department of Neurobiology and Anatomy, MD., PhD. Professor (10220534)
OSAKO Yoji Kochi University, Department of Neurobiology and Anatomy, PhD. Assistant Professor (40335922)
ADACHI Kiyomi Kochi University, Department of Neurobiology and Anatomy, PhD. Assistant Professor (60335932)
HOSOKAWA Takatoshi Kochi University, Department of Pediatrics, MD., PhD. Assistant Professor (10380312)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Mental retardation / Developmental disorder / Serine protease / Neurotrvpsin / Social behavior / Learning and memory |
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| Research Abstract |
Our aim is the development of novel therapy and diagnostic method for developmental disorders based on the molecular mechanism of the disease. In this study, we analyzed 1) the behavioral phonotype of mice lacking a mental retardation gene, motopsin (prss12), and 2) spatio-temporal localization of a motopsin-interacting protein, SEZ6.
Motopsin-deficient mice showed moderately impaired spatial memory. A social memory test failed to reveal abnormality, however, the mutant mice showed prolonged sniffing to a stranger mouse. In a social novelty test, motopsin-deficient mice showed prolonged interest even in a familiar mouse. Consistent with such behavioral deficits, the spine density on apical dendrites of pyramidal neurons was significantly decreased at hippocampus CA1 region, which is known to be crucial for spatial memory and social behavior.
We have previously identified SEZ6 as a motopsin-binding protein. SEZ6 immunoreactivity (IR) was detected at the hippocampal CA1 region, cerebral cortex, lateral amygdala, and caudate putamen using anti-SEZ6 antibody, which was prepared against recombinant SEZ6 protein. It was noted that SEZ6 IR was obvious in the cerebral cortex at postnatal day (P) 7 and the CA1 hippocampus at P10, suggesting interaction with motopsin in these regions. Similar localization was observed in the human brain and spinal cord.
Our results suggest that motopsin secreted from neuronal cells anchors to SEZ6 proteins on neurons and that lack of motopsin function causes some symptom of mental retardation, eg, impaired memory formation and abnormal social behavior, through the defect of hippocampal function.
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Report
(3 results)
Research Products
(36 results)
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[Journal Article] Multiple promoters regulate tissue-specific alternative splicing of the human kallikrein gene,KLK11/hippostasin2006
Author(s)
Mitsui, S., Nakamura, T., Okui, A., Kominami, K., Uemura, H., Yamaguchi, N.
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Journal Title
FEBS Journal 273
Pages: 3678-3686
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Multiple promoters regulate tissue-specific alternative splicing of the human kallikrein gene, KLK11/hippostasin.2006
Author(s)
Mitsui., S., Nakamura, T., Okui, A., Kominami, K., Uemura, H., Yamaguchi, N
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Journal Title
FEBS Journal 273
Pages: 3678-3686
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Multiple promoters regulate tissue-specific alternative splicing of the human kallikrein gene, KLK11/hippostasin.2006
Author(s)
Mitsui, S., Nakamura, T., Okui, A., Kominami, K., Uemura, H., Yamaguchi, N.
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Journal Title
FEBS Journal 273
Pages: 3678-3686
Related Report
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[Presentation] Localization of motopsin-interacting protein, Sez-6, in the mouse brain.2007
Author(s)
Mitsui., S., Adachi, K., Osako, Y., Yuri, K
Organizer
The 112th annual meeting of the Japanese Association of Anatomies
Place of Presentation
Osaka, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Decreased spine density of pyramidal neurons of mice lacking a mental retardation gene, motopsin/neurotrypsin.2007
Author(s)
Mitsui., S., Osako, Y., Yuri, K., Yokoi, F., Dang, M. T., Li, Y., Yamaguchi
Organizer
The 30th annual meeting of the Japan Neuroscience Society
Place of Presentation
Yokohama, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] A mental retardation gene, motopsin, modulates social behavior.2007
Author(s)
Mitsui., S., Osako, Y., Yuri, K., Yokoi, F., Dang, M. T., Li, Y., Yamaguchi, N
Organizer
BMB2007
Place of Presentation
Yokohama, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Motopsin/neurotrypsin (PRSS12), a mental retardation gene, interacts with seizure-related protein 6.2006
Author(s)
Mitsui, S., Adachi, K., Osako, Y., Yuri, K
Organizer
Neuroscience 2006
Place of Presentation
Atlanta, USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Decreased spine density of pyramidal neurons of mice lacking a mental retardation gene, motopsin/neurotrypsin.2006
Author(s)
Mitsui., S., Osako, Y., Yuri, K., Yokoi, F., Dang, M. T., Li, Y., Yamaguchi, N
Organizer
The 29th Annual Meeting of the Japan Neuroscience Society
Place of Presentation
Kyoto, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Mild impairment of memory and social behavior of the mice lacking a mental retardation gene, motormin/neurotryosin.2006
Author(s)
Osako, Y., Mitsui, S., Yuri, K., Yokoi, F., Dang, M. T., Li, Y., Yamaguchi, N
Organizer
The 29th Annual Meeting of the Japan Neuroscience Society
Place of Presentation
Kyoto, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Abnormal social behavior and decreased spine density of the mice lacking a mental retardation gene, motopsin (prssl2).2006
Author(s)
Osako, Y., Mitsui, S., Yuri, K., Yokoi, F., Dang, M. T., Li, Y., Yamaguchi, N
Organizer
MBSJ forum 2006 ; Molecular Biology-tthe Next decade-Conference & Scientific Exhibition
Place of Presentation
Nagoya, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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